title: Mitochondria in chemotherapy-induced apoptosis: a prospective novel target of cancer therapy (review).
abstract: Resistance to apoptosis is a frequent characteristic of cancer cells and participates both in the initial phase of carcinogenesis and in the development of chemotherapy resistance. Recently, it has become clear that a disruption in mitochondrial membrane function is a decisive event of the apoptotic process leading to the disposal of chemotherapy-treated cells. Opening of the mitochondrial megachannel (also called permeability transition pore) is at least in part responsible for the disruption of mitochondrial membrane integrity in apoptosis. The megachannel is regulated by numerous endogenous effectors including members of the Bcl-2/Bax family, the redox status of the cell, cytosolic Ca2+ levels, ceramide, and amphipathic peptides. Chemotherapeutic agents may induce opening of the megachannel by modulating some of these endogenous effectors. The disruption of mitochondrial membrane integrity involves a loss of metabolic functions and the liberation of intermembrane proteins into the cytosol. Such proteins, which normally are well secluded in mitochondria, include cytochrome c and AIF (apoptosis inducing factor), which both activate caspases and endonucleases upon release into the cytosol. Strategies for the development of chemotherapeutic agents acting on mitochondria are discussed.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Propre de Recherche 420, 19 rue Guy Môquet, F-94801 Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Decaudin
authors.forename: I
authors.initials: I
authors.lastname: Marzo
authors.forename: C
authors.initials: C
authors.lastname: Brenner
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2